Mechanisms of disease during embryogenesis Flashcards
In human development, what are the 2 main periods?
- Embryonic period:
→ Up to the end of week 8
→ Most of the organogenesis occurs in these first 8 weeks
→ i.e. ‘body plan’ - Fetal period:
→ The remaining time in utero
→ Involves growth and modelling
→ i.e. refinement
Defects during embryogenesis result in congenital malformations
What are the overall stages an egg goes through to develop into an adult?
From egg —> to adult stages:
- Fertilisation
- Cleavage
- Gastrulation
- Neurulation and somitogenesis
- Organogenesis
Where does fertilisation occur?
In the fallopian duct, (ampullary region)
Before the development of the embryo proper, the conceptus must first implant, then generate the “germ” disc. This takes ~10 days.
What are the main components of a fertilised egg?
→ Haploid pronuclei: one from oocyte and one from sperm
→ Two polar bodies from oocyte formation
→ Zona pellucida and excluded spermatozoa
→ Cumulus cells surrounding
When does cleavage occur? What is the process of cleavage?
(part 1)
→ The cell is undergoing a series of cleaves before entering the uterus (i.e. in the fallopian tube)
→ Cleavage - splitting (the zygote) without growth so must happen quickly
→ The 2 cell zygote divides into 4 cell zygote etc and then once it reaches 8-16 cells, it is called a morula.
What is the process of cleavage?
(part 2)
→ Zygote at 8-16 cells, known as a MORULA (usually day 3)
→ Ready to undergo its first reorganisation - called COMPACTION
→ During compaction, some cells in the embryo remain in the exterior of the embryo and some to the interior
→ Interior cells are apolar - all their sites are in contact with other sites; they don’t have any surface that is free
→ Exterior cells give rise to the TROPHECTODERM and the cells on the interior give rise to the inner cell mass
→ The outside cells start pumping fluid to the inside which leads to the formation of a fluid filled cavity inside the embryo called the BLASTOCOELE
→ The blastocoele pushes the inner cell mass towards one side and gives an asymmetry to the embryo.
→ Now it is called a BLASTOCYST
→ Once it has divided into 32-64 cells, it is known as a blastocyst (usually day 4/5)
→ The blastocyst by now has reached the uterus and is ready to implant in the uterine wall.
What is the process of cleavage, inner cell mass specific?
(part 3 - last part)
Inner cell mass gives rise to 2 types of cells:
→ Cells on the edge (dark purple in a line in the image) between the inner cell mass and blastocoele and the group of inner cells that do not come into contact with the blastocoele
→ This gives rise to the HYPOBLAST and the EPIBLAST
So now you can identify the bilaminar germ disc:
→ Epiblast-coming from inner cell mass
→ Hypoblast on the outer (dark purple), epiblast seen on next slide as beige.
→ The EPIBLAST cells arrange themselves so that they give rise to another cavity which will become the amniotic cavity
→ The embryo is now ready to undergo the second main reorganisation - GASTRULATION.
What is gastrulation?
What occurs in the Gastrulation stage?
→ Gastrulation is the process where the bilaminar embryonic disc (consisting of the hypoblast and epiblast) undergoes reorganisation to form a trilaminar disc (3 primary germ layers), so the cell goes from being 2 layers to 3 layers
BILAMINAR GERM DISK –> TRILAMINAR DISC
- Cells in the epiblast through a primitive groove will displace cells in the hypoblast, forming the MESODERM and ENDODERM
(Hypoblast, primitive endoderm, is displaced by involuting cells that become definitive endoderm and mesoderm)
The remaining cells of epiblast that didn’t ingress into the hypoblast give rise to ECTODERM - now there are all 3 layers and ready for NEURULATION.
Summary from video of Gastrulation:
→ The first cells to invaginate through the primitive groove form the definitive endoderm
→ The endoderm is responsible for the formation of the GI tract
→ The remaining cells of the epiblast are called the ectoderm
→ Cells that remain in the space between the definitive endoderm and definitive ectoderm form a layer called the mesoderm.
(https://www.youtube.com/watch?v=ADlYn0ImTNg&t=103s&ab_channel=PrimalPictures3DAnatomy%26Physiology)
What occurs in neurulation?
→ The notochordal process is source of neural inducers.
→ The primitive streak moves up and then comes back down, laying down the notochord for formation.
NOTOCHORD- rod of cells which secrete various extracellular molecules that will instruct the ectoderm to become neural tissue and neural plate is established.
→ As the primitive streak regresses, the notochord is extended posteriorly and instructs neural plate formation (now at 21 days).
→ Neural folds then meet and fuse to create a neural tube
What happens between days 20-22 during neurulation?
Cell reorganisation also occurs too here.
Mesodermal cells start to become segmented in tissue blocks called SOMITES. (precursors of bones and muscles)
Neurulation is concomitant with other form-shaping (morphogenetic) processes, particularly gut formation and body folding (“silk purse” model).
Folding leads to the formation of the umbilical cord.
What occurs in Organogenesis?
Differentiation of somitic derivatives
→ bones, muscles, tendons
Development of sensory organs
→ ears, eyes, olfactory pits
Limb formation
→ forelimbs first, hind-limbs next
→ establishment of pattern in the limbs: proximodistal, anterior-posterior, dorsal-ventral
Formation of face structures
→ jaws, nose, tongue, palate
Formation of genital structures
Classification of causes of disease
→ Single gene mutations: refers to the cases when mutation in one particular gene will be enough to display a characteristic defect.
→ Chromosomal anomalies: in some cases, rather than single mutations, whole chromosomal rearrangements are responsible for a disease.
→ The most obvious examples are chromosomal trisomies, such as trisomy of chromosome 21, leading to Down syndrome.
Polygenic disorders: refers to cases where it is not just one gene affected, but several different genes simultaneously affected, what causes the disease.
Environmental factors: refers to the deleterious influence of the environment on a particular process. These can be very diverse: diet, infection, toxic compounds.
Summary of the above lecture
→ Human embryonic development is a very complex process, controlled by networks of genes acting together.
→ Defects in gene function during this process will result in defective embryonic development.
→ Some genes are needed at several different stages of embryonic development, or in several organs.
→ Alterations in the function of such genes will result in complex phenotypes in a variety of tissues. These are called syndromic diseases.
→ Embryonic development can also be perturbed by environmental insults, maternal diet deficiencies or infections during pregnancies. Often, it is a combination of genetic and environmental causes what results in congenital disease.
→ Identifying the relative contribution of these factors is a challenging and often very difficult process.
Define single gene mutations
→ Refers to the cases when mutation in one particular gene will be enough to display a characteristic defect
Define chromosomal anomalies
→ In some cases, rather than single mutations, whole chromosomal rearrangements are responsible for a disease
→ The most obvious examples are chromosomal trisomies, such as trisomy of chromosome 21, leading to Down syndrome
